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2.
Psychiatry Res ; 299: 113837, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33721783

RESUMO

ABO blood types and their corresponding antigens have long been assumed to be related to different human diseases. So far, smaller studies on the relationship between mental disorders and blood types yielded contradicting results. In this study we analyzed the association between ABO blood types and lifetime major depressive disorder (MDD). We performed a pooled analysis with data from 26 cohorts that are part of the MDD working group of the Psychiatric Genomics Consortium (PGC). The dataset included 37,208 individuals of largely European ancestry of which 41.6% were diagnosed with lifetime MDD. ABO blood types were identified using three single nucleotide polymorphisms in the ABO gene: rs505922, rs8176746 and rs8176747. Regression analyses were performed to assess associations between the individual ABO blood types and MDD diagnosis as well as putative interaction effects with sex. The models were adjusted for sex, cohort and the first ten genetic principal components. The percentage of blood type A was slightly lower in cases than controls while blood type O was more prominent in cases. However, these differences were not statistically significant. Our analyses found no evidence of an association between ABO blood types and major depressive disorder.

3.
Transl Psychiatry ; 11(1): 192, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33782385

RESUMO

A retrospective meta-analysis of magnetic resonance imaging voxel-based morphometry studies proposed that reduced gray matter volumes in the dorsal anterior cingulate and the left and right anterior insular cortex-areas that constitute hub nodes of the salience network-represent a common substrate for major psychiatric disorders. Here, we investigated the hypothesis that the common substrate serves as an intermediate phenotype to detect genetic risk variants relevant for psychiatric disease. To this end, after a data reduction step, we conducted genome-wide association studies of a combined common substrate measure in four population-based cohorts (n = 2271), followed by meta-analysis and replication in a fifth cohort (n = 865). After correction for covariates, the heritability of the common substrate was estimated at 0.50 (standard error 0.18). The top single-nucleotide polymorphism (SNP) rs17076061 was associated with the common substrate at genome-wide significance and replicated, explaining 1.2% of the common substrate variance. This SNP mapped to a locus on chromosome 5q35.2 harboring genes involved in neuronal development and regeneration. In follow-up analyses, rs17076061 was not robustly associated with psychiatric disease, and no overlap was found between the broader genetic architecture of the common substrate and genetic risk for major depressive disorder, bipolar disorder, or schizophrenia. In conclusion, our study identified that common genetic variation indeed influences the common substrate, but that these variants do not directly translate to increased disease risk. Future studies should investigate gene-by-environment interactions and employ functional imaging to understand how salience network structure translates to psychiatric disorder risk.

4.
BMC Med ; 19(1): 38, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33583409

RESUMO

BACKGROUND: Neurofilament light chain (NfL) is a cytoskeletal protein component whose release into blood is indicative of neuronal damage. Tau is a microtubule-associated protein in neurons and strongly associated with overall brain degeneration. NfL and tau levels are associated with mortality in different neurological diseases, but studies in the general population are missing. We investigated whether NfL and tau serum levels could serve as prognostic markers for overall mortality in elderly individuals without pre-defined neurological conditions. Further, we investigated the cross-sectional associations between NfL, tau, neuropsychological functioning, and brain structures. METHODS: In 1997, 385 inhabitants of Augsburg who were aged 65 years and older were included in the Memory and Morbidity in Augsburg Elderly (MEMO) study. They participated in a face-to-face medical interview including neuropsychological tests and magnetic resonance imaging (MRI) of the brain. NfL and tau were measured from non-fasting blood samples using highly sensitive single molecule array assays. To assess the prognostic accuracy of the biomarkers, concordance statistics based on the predicted 5-year survival probabilities were calculated for different Cox regression models. Associations between the biomarkers and the neuropsychological test scores or brain structures were investigated using linear or logistic regression. RESULTS: NfL (HR 1.27, 95% CI [1.14-1.42]) and tau (1.20 [1.07-1.35]) serum levels were independently associated with all-cause mortality. NfL, but not tau, increased the prognostic accuracy when added to a model containing sociodemographic characteristics (concordance statistic 0.684 [0.612-0.755] vs. 0.663 [0.593-0.733]), but not when added to a model containing sociodemographic characteristics and brain atrophy or neuropsychological test scores. NfL serum levels were cross-sectionally associated with neuropsychological test scores and brain structures. CONCLUSIONS: The association between NfL serum levels and brain atrophy and neuropsychological performance in individuals without overt neurological disease is similar to that seen in patients with neurodegenerative diseases. These findings support the concept of a continuum of physiological aging and incipient, subclinical pathology, and manifest disease. NfL, but not tau, serum levels might serve as a prognostic marker for all-cause mortality if no other clinical information is available.

5.
J Clin Sleep Med ; 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33599203

RESUMO

STUDY OBJECTIVES: To evaluate inter-rater reliability (IRR) between manual sleep stage scoring performed in two European sleep centers and automatic sleep stage scoring performed by the previously validated artificial intelligence-based Stanford-STAGES algorithm (Stephansen et al., 2018). METHODS: Full night polysomnographies of 1066 participants were included. Sleep stages were manually scored in Berlin and Innsbruck sleep centers and automatically scored with the Stanford-STAGES algorithm. For each participant, we compared 1) Innsbruck to Berlin scorings (INN vs BER); 2) Innsbruck to automatic scorings (INN vs AUTO); 3) Berlin to automatic scorings (BER vs AUTO); 4) epochs where scorers from Innsbruck and Berlin had consensus to automatic scoring (CONS vs AUTO); and 5) both Innsbruck and Berlin manual scorings (MAN) to the automatic ones (MAN vs AUTO). IRR was evaluated with several measures, including overall and sleep stage-specific Cohen's kappa (κ). RESULTS: Overall agreement across participants was substantial for INN vs BER (κ=0.66±0.13), INN vs AUTO (κ=0.68±0.14), CONS vs AUTO (κ=0.73±0.14) and MAN vs AUTO (κ=0.61±0.14), and moderate for BER vs AUTO (κ=0.55±0.15). Human scorers had the highest disagreement for N1 sleep (κN1=0.40±0.16 for INN vs BER). Automatic scoring had lowest agreement with manual scorings for N1 and N3 sleep (κN1=0.25±0.14 and κN3=0.42±0.32 for MAN vs AUTO). CONCLUSIONS: IRR for sleep stage scoring between human scorers was in line with previous findings and the algorithm achieved an overall substantial agreement with manual scoring. In this cohort, the Stanford-STAGES algorithm showed similar performances to the ones achieved in the original study, suggesting that it is generalizable to new cohorts. Before its integration in clinical practice, future independent studies should further evaluate it in other cohorts.

6.
Nat Commun ; 12(1): 1152, 2021 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608538

RESUMO

The humoral immune response to SARS-CoV-2 is a benchmark for immunity and detailed analysis is required to understand the manifestation and progression of COVID-19, monitor seroconversion within the general population, and support vaccine development. The majority of currently available commercial serological assays only quantify the SARS-CoV-2 antibody response against individual antigens, limiting our understanding of the immune response. To overcome this, we have developed a multiplex immunoassay (MultiCoV-Ab) including spike and nucleocapsid proteins of SARS-CoV-2 and the endemic human coronaviruses. Compared to three broadly used commercial in vitro diagnostic tests, our MultiCoV-Ab achieves a higher sensitivity and specificity when analyzing a well-characterized sample set of SARS-CoV-2 infected and uninfected individuals. We find a high response against endemic coronaviruses in our sample set, but no consistent cross-reactive IgG response patterns against SARS-CoV-2. Here we show a robust, high-content-enabled, antigen-saving multiplex assay suited to both monitoring vaccination studies and facilitating epidemiologic screenings for humoral immunity towards pandemic and endemic coronaviruses.


Assuntos
Anticorpos Antivirais/imunologia , /imunologia , Reações Cruzadas , Imunidade Humoral , /diagnóstico , Humanos , Imunoensaio , Imunoglobulina G/imunologia , Fosfoproteínas/imunologia , Sensibilidade e Especificidade , Glicoproteína da Espícula de Coronavírus/imunologia
7.
Stroke ; 52(2): 406-415, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33493053

RESUMO

BACKGROUND AND PURPOSE: Men and women are differently affected by acute ischemic stroke (AIS) in many aspects. Prior studies on sex disparities were limited by moderate sample sizes, varying years of data acquisition, and inconsistent inclusions of covariates leading to controversial findings. We aimed to analyze sex differences in AIS severity, treatments, and early outcome and to systematically evaluate the effect of important covariates in a large German stroke registry. METHODS: Analyses were based on the Stroke Registry of Northwestern Germany from 2000 to 2018. We focused on admission-stroke severity and disability, acute recanalization treatment, and early stroke outcomes. Potential sex divergences were investigated via odds ratio (OR) using logistic regression models. Covariates were introduced in 3 steps: (1) base models (age and admission year), (2) partially adjusted models (additionally corrected for acute stroke severity and recanalization treatment), (3) fully adjusted models (additionally adjusted for onset-to-admission time interval, prestroke functional status, comorbidities, and stroke cause). Models were separately fitted for the periods 2000 to 2009 and 2010 to 2018. RESULTS: Data from 761 106 patients with AIS were included. In fully adjusted models, there were no sex differences with respect to treatment with intravenous thrombolysis (2000-2009: OR, 0.99 [95% CI, 0.94-1.03]; 2010-2018: OR, 1.0 [0.98-1.02]), but women were more likely to receive intraarterial therapy (2010-2018: OR, 1.12 [1.08-1.15]). Despite higher disability on admission (2000-2009: OR, 1.10 [1.07-1.13]; 2010-2018: OR, 1.09 [1.07-1.10]), female patients were more likely to be discharged with a favorable functional outcome (2003-2009: OR, 1.05 [1.02-1.09]; 2010-2018: OR, 1.05 [1.04-1.07]) and experienced lower in-hospital mortality (2000-2009: OR, 0.92 [0.86-0.97]; 2010-2018: OR, 0.91 [0.88-0.93]). CONCLUSIONS: Female patients with AIS have a higher chance of receiving intraarterial treatment that cannot be explained by clinical characteristics, such as age, premorbid disability, stroke severity, or cause. Women have a more favorable in-hospital recovery than men because their higher disability upon admission was followed by a lower in-hospital mortality and a higher likelihood of favorable functional outcome at discharge after adjustment for covariates.

8.
Mult Scler ; : 1352458520985118, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33467978

RESUMO

BACKGROUND: Newly approved, drug-modifying therapies are associated with still unknown adverse events, although clinical trials leading to approval have strict inclusion and exclusion criteria and analyse safety and efficacy. OBJECTIVES: The aim of this study was to analyse the eligibility of multiple sclerosis (MS) patients treated in routine care into the phase III clinical trial of the respective drug. METHODS: In total, 3577 MS patients with 4312 therapies were analysed. Patients with primary-progressive MS were excluded. Inclusion and exclusion criteria of phase III clinical trials in relapsing-remitting MS were adopted and subsequently applied. A comparison in clinical and sociodemographic characteristics was made between patient who met the criteria and those who did not. RESULTS: 83% of registered patients would not have been eligible to the respective phase III clinical trial. Relapse was the single most frequent criterion not fulfilled (74.7%), followed by medication history (21.2%). CONCLUSION: The majority of MS patients treated in routine care would not have met clinical trials criteria. Thus, the efficacy and safety of therapies in clinical trials can differ from those in the real world. Broader phase III inclusion criteria would increase their eligibility and contribute to a better generalizability of the results in clinical trials.

9.
Dtsch Arztebl Int ; 117(50): 861-867, 2020 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-33295275

RESUMO

BACKGROUND: The pandemic caused by the coronavirus SARS-CoV-2 and the countermeasures taken to protect the public are having a substantial effect on the health of the population. In Germany, nationwide protective measures to halt the spread of the virus were implemented in mid-March for 6 weeks. METHODS: In May, the impact of the pandemic was assessed in the German National Cohort (NAKO). A total of 113 928 men and women aged 20 to 74 years at the time of the baseline examination conducted 1 to 5 years earlier (53%) answered, within a 30-day period, a follow-up questionnaire on SARS-CoV-2 test status, COVID-19- associated symptoms, and self-perceived health status. RESULTS: The self-reported SARS-CoV-2 test frequency among the probands was 4.6%, and 344 participants (0.3%) reported a positive test result. Depressive and anxiety-related symptoms increased relative to baseline only in participants under 60 years of age, particularly in young women. The rate of moderate to severe depressive symptoms increased from 6.4% to 8.8%. Perceived stress increased in all age groups and both sexes, especially in the young. The scores for mental state and self-rated health worsened in participants tested for SARS-CoV-2 compared with those who were not tested. In 32% of the participants, however, self-rated health improved. CONCLUSION: The COVID-19 pandemic and the protective measures during the first wave had effects on mental health and on self-rated general health.

10.
Nutr Neurosci ; : 1-10, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33295833

RESUMO

Background: Vitamin D deficiency has been suggested to contribute to the onset of depression, but published results are inconsistent. The aims of this study were 1) to compare serum 25-hydroxyvitamin D (25(OH)D) levels in patients with depression and non-depressed controls and 2) to examine whether distinct subtypes and symptom severity of depression may vary in their association with 25(OH)D. Methods: The study involved cross-sectional data of n=1169 participants from the BiDirect Study (n=639 patients with clinically diagnosed major depressive disorder (MDD), n=530 controls). Serum 25(OH)D was measured via LS-MS/MS. We performed analysis of covariance to evaluate adjusted means of 25(OH)D levels and multinomial logistic regression to assess the association of depression and its clinical characteristics, namely distinct subtypes and symptom severity, with 25(OH)D status (adjusted for age, sex, education, season of blood sample collection, and lifestyle factors). Results: In total, 45.0% of the participants had adequate 25(OH)D levels (≥20 ng/ml), whereas 24.9% had a deficiency (<12 ng/ml). Patients with MDD had lower 25(OH)D levels than controls (16.7 vs. 19.6 ng/ml, p<0.001). Patients with atypical depression had the lowest levels (14.6 ng/ml). Symptom severity was inversely related to 25(OH)D. Moreover, patients with MDD had a more than 2-times higher odds of 25(OH)D deficiency than controls. Atypical depression showed the highest odds of deficiency. Conclusions: The results support that patients with depression have lower 25(OH)D concentrations than non-depressed individuals. Distinct subtypes, particularly the atypical subtype, may play a special role in this context. Therefore, depression heterogeneity should be considered in future research.

11.
BMC Psychol ; 8(1): 118, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33160414

RESUMO

BACKGROUND: The perception of the affective quality of stimuli with regard to valence and arousal has mostly been studied in laboratory experiments. Population-based research may complement such studies by accessing larger, older, better balanced, and more heterogeneous samples. Several characteristics, among them age, sex, depression, or anxiety, were found to be associated with affective quality perception. Here, we intended to transfer valence and arousal rating methods from experimental to population-based research. Our aim was to assess the feasibility of obtaining and determining the structure of valence and arousal ratings in the setting of the large observational BiDirect Study. Moreover, we explored the roles of age, sex, depression, and anxiety for valence and arousal ratings of words. METHODS: 704 participants provided valence and arousal ratings for 12 written nouns pre-categorized as unpleasant, neutral, or pleasant. Predictors of valence and arousal ratings (i.e. age, sex, depression, and anxiety) were analyzed for six outcomes that emerge by combining two affective dimensions with three words categories. Data were modeled with multiple linear regression. Relative predictor importance was quantified by model-explained variance decomposition. RESULTS: Overall, average population-based ratings replicated those found in laboratory settings. The model did not reach statistical significance in the valence dimension. In the arousal dimension, the model explained 5.4% (unpleasant), 4.6% (neutral), and 3.5% (pleasant) of the variance. (Trend) effects of sex on arousal ratings were found in all word categories (unpleasant: increased arousal in women; neutral, pleasant: decreased arousal in women). Effects of age and anxiety (increased arousal) were restricted to the neutral words. CONCLUSIONS: We report results of valence and arousal ratings of words in the setting of a large, observational, population-based study. Method transfer yielded acceptable data quality. The analyses demonstrated small effects of the selected predictors in the arousal dimension.


Assuntos
Envelhecimento/psicologia , Ansiedade/psicologia , Nível de Alerta , Depressão/psicologia , Emoções , Idioma , Caracteres Sexuais , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais
12.
Drug Saf ; 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33098059

RESUMO

The long-term and potential rare side effects of new immunomodulating drugs for the treatment of multiple sclerosis (MS) are often not well known. Spontaneous case report systems of adverse drug effects are a valuable source in pharmacovigilance, but have several limitations. Primary data collections within registries allow a comprehensive analysis of potential side effects, but face several challenges. This article will outline the chances and challenges of registry-based adverse event reporting, using the example of the German immunotherapeutic registry REGIMS. REGIMS is an observational, clinical multicenter registry that aims to assess the incidence, type, and consequences of side effects of MS immunotherapies. Patients treated with an approved MS medication are recruited by their physicians during routine visits in hospitals, outpatient clinics, and MS-specialized practices. REGIMS incorporates an electronic physician-based documentation in each center and a paper-based patient documentation, both at baseline and regular follow-up visits. By the end of 2019, 43 REGIMS centers were actively recruiting patients and performing follow-up documentations. The majority of the first 1000 REGIMS patients were female (69.3%), had relapse-remitting MS (89.8%), and were treated with a second-line therapy. During the implementation of REGIMS, several logistic and procedural challenges had to be overcome, which are outlined in this paper. Pharmacovigilance registries such as REGIMS provide high-quality primary data from a specific patient population in a real-world care setting and enable pharmacovigilance research that cannot be carried out using secondary data. Despite the logistic and procedural challenges in establishing a multicenter pharmacovigilance registry in Germany, the advantages outweigh the drawbacks.

13.
Front Neurol ; 11: 996, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013658

RESUMO

Daclizumab was approved by the FDA and the EMA in 2016 for the treatment of relapsing forms of multiple sclerosis (MS). Cases of severe inflammatory brain disease with fatal outcome led to the withdrawal of approval in Europe and the US on March 2, 2018. Approximately 8,000 patients worldwide received daclizumab, but little is known about the further therapy management of these patients after the withdrawal of daclizumab. The aim of this study is to further analyze therapy management in MS patients after safety warnings and market withdrawal. Data from two registries in Germany, the German MS Registry (GMSR) and REGIMS, were used for this analysis. In total, 267 patients were included in this study. For almost 25% of patients (in the GMSR) daclizumab was the initial treatment. Most common pre-treatments were fingolimod, dimethyl fumarate, and natalizumab; various injectables summed up to 25.9%. The most common follow-up therapies were ocrelizumab and fingolimod. In most patients, follow-up therapies were administered shortly after discontinuation of daclizumab. The wash-out time for subsequent therapies varied between 1.2 and 4.0 months. Warnings and decisions by authorities led to a rapid decline and termination of therapies in both cohorts, indicating that such warnings have an immediate impact on the treatment landscape. Therapies that were started within a short time after the discontinuation of daclizumab were subsequently replaced by other therapies and may be considered as bridging therapies.

14.
Stroke ; 51(12): 3664-3672, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33040703

RESUMO

BACKGROUND AND PURPOSE: Quality indicators (QI) are an accepted tool to measure performance of hospitals in routine care. We investigated the association between quality of acute stroke care defined by overall adherence to evidence-based QI and early outcome in German acute care hospitals. METHODS: Patients with ischemic stroke admitted to one of the hospitals cooperating within the ADSR (German Stroke Register Study Group) were analyzed. The ADSR is a voluntary network of 9 regional stroke registers monitoring quality of acute stroke care across 736 hospitals in Germany. Quality of stroke care was defined by adherence to 11 evidence-based indicators of early processes of stroke care. The correlation between overall adherence to QI with outcome was investigated by assessing the association between 7-day in-hospital mortality with the proportion of QI fulfilled from the total number of QI the individual patient was eligible for. Generalized linear mixed model analysis was performed adjusted for the variables age, sex, National Institutes of Health Stroke Scale and living will and as random effect for the variable hospital. RESULTS: Between 2015 and 2016, 388 012 patients with ischemic stroke were reported (median age 76 years, 52.4% male). Adherence to distinct QI ranged between 41.0% (thrombolysis in eligible patients) and 95.2% (early physiotherapy). Seven-day in-hospital mortality was 3.4%. The overall proportion of QI fulfilled was median 90% (interquartile range, 75%-100%). In multivariable analysis, a linear association between overall adherence to QI and 7-day in-hospital-mortality was observed (odds ratio adherence <50% versus 100%, 12.7 [95% CI, 11.8-13.7]; P<0.001). CONCLUSIONS: Higher quality of care measured by adherence to a set of evidence-based process QI for the early phase of stroke treatment was associated with lower in-hospital mortality.

16.
Sleep ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33029624

RESUMO

STUDY OBJECTIVES: Sleep is essential for restorative metabolic changes and its physiological correlates can be examined using overnight polysomnography. However, the association between physiological sleep characteristics and brain structure is not well understood. We aimed to investigate gray matter volume and cognitive performance related to physiological sleep characteristics. METHODS: Polysomnographic recordings from 190 community-dwelling participants were analyzed with a principal component analysis in order to identify and aggregate shared variance into principal components. The relationship between aggregated sleep components and gray matter volume was then analyzed using voxel-based morphometry. In addition, we explored how cognitive flexibility, selective attention and semantic fluency were related to aggregated sleep components and gray matter volume. RESULTS: Three principal components were identified from the polysomnographic recordings. The first component, primarily described by apnea events and cortical arousal, was significantly associated with lower gray matter volume in the left frontal pole. This apnea-related component was furthermore associated with lower cognitive flexibility and lower selective attention. CONCLUSIONS: Sleep disrupted by cortical arousal and breathing disturbances is paralleled by lower gray matter volume in the frontal pole, a proposed hub for the integration of cognitive processes. The observed effects provide new insights on the interplay between disrupted sleep, particularly breathing disturbances and arousal, and the brain.

17.
Sleep ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33017007

RESUMO

Advanced brain ageing is commonly regarded as a risk factor for neurodegenerative diseases, e.g. Alzheimer's dementia, and it was suggested that sleep disorders such as obstructive sleep apnoea (OSA) are significantly contributing factors to these neurodegenerative processes. To determine the association between OSA and advanced brain ageing, we investigated the specific effect of two indices quantifying OSA, namely the apnoea-hypopnea index (AHI) and the oxygen desaturation index (ODI), on brain age, a score quantifying age-related brain patterns in 169 brain regions, using magnetic resonance imaging and overnight polysomnography data from 690 participants (48.8% women, mean age 52.5±13.4 years) of the Study of Health in Pomerania. We additionally investigated the mediating effect of subclinical inflammation parameters on these associations via a causal mediation analysis. AHI and ODI were both positively associated with brain age (AHI std. effect [95% CI]: 0.07 [0.03; 0.12], p-value: 0.002; ODI std. effect [95% CI]: 0.09 [0.04; 0.13], p-value: <0.0003). The effects remained stable in the presence of various confounders such as diabetes and were partially mediated by the white blood cell count, indicating a subclinical inflammation process. Our results reveal an association between OSA and brain age, indicating subtle but widespread age-related changes in regional brain structures, in one of the largest general population studies to date, warranting further examination of OSA in the prevention of neurodegenerative diseases.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33088336

RESUMO

Background: The Functioning Assessment Short Test (FAST) is an interviewer-administered scale assessing functional impairment originally developed for psychiatric patients. Objectives: To adapt the FAST for the general population, we developed a self-administered version of the scale and assessed its properties in a pilot study. Methods: The original FAST scale was translated into German via forward and backward translation. Afterwards, we adjusted the scale for self-administered application and inquired participants from two ongoing studies in Germany, 'STAAB' (Würzburg) and 'BiDirect' (Münster), both recruiting subjects from the general population across a wide age range (STAAB: 30-79 years, BiDirect: 35-65 years). To assess reliability, agreement of self-assessment with proxy-assessment by partners was measured via intraclass correlation coefficient (ICC) over the FAST score. Construct validity was estimated by conducting correlations with validated scales of depression (PHQ-9), anxiety (GAD-7), and health-related quality of life (SF-12) and regression analyses using these scales besides potentially disabling comorbidities (e.g. Chronic Back Pain (CBP)). Results: Participants (n=54) had a median age of 57.0 years (quartiles: 49.8, 65.3), 46.3% were female. Reliability was moderate: ICC 0.50 (95% CI 0.46-0.54). The FAST score significantly correlated with PHQ-9, GAD-7, and the mental sub-scale of SF-12. In univariable linear regression, all three scales and chronic back pain explained variance of the FAST score. In multivariable analysis, only CBP and the SF-12 remained significant predictors. Conclusion: The German self-administered version of the FAST yielded moderate psychometric properties in this pilot study, indicating its applicability to assess functional impairment in the general population.

20.
Biol Psychiatry ; 88(9): 678-686, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32646651

RESUMO

BACKGROUND: Neuroimaging studies have consistently reported similar brain structural abnormalities across different psychiatric disorders. Yet, the extent and regional distribution of shared morphometric abnormalities between disorders remains unknown. METHODS: Here, we conducted a cross-disorder analysis of brain structural abnormalities in 6 psychiatric disorders based on effect size estimates for cortical thickness and subcortical volume differences between healthy control subjects and psychiatric patients from 11 mega- and meta-analyses from the ENIGMA (Enhancing Neuro Imaging Genetics Through Meta Analysis) consortium. Correlational and exploratory factor analyses were used to quantify the relative overlap in brain structural effect sizes between disorders and to identify brain regions with disorder-specific abnormalities. RESULTS: Brain structural abnormalities in major depressive disorder, bipolar disorder, schizophrenia, and obsessive-compulsive disorder were highly correlated (r = .443 to r = .782), and one shared latent underlying factor explained between 42.3% and 88.7% of the brain structural variance of each disorder. The observed shared morphometric signature of these disorders showed little similarity with brain structural patterns related to physiological aging. In contrast, patterns of brain structural abnormalities independent of all other disorders were observed in both attention-deficit/hyperactivity disorder and autism spectrum disorder. Brain regions showing high proportions of independent variance were identified for each disorder to locate disorder-specific morphometric abnormalities. CONCLUSIONS: Taken together, these results offer novel insights into transdiagnostic as well as disorder-specific brain structural abnormalities across 6 major psychiatric disorders. Limitations comprise the uncertain contribution of risk factors, comorbidities, and medication effects to the observed pattern of results that should be clarified by future research.

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